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A Peer-Reviewed Newsletter Issue 7

December 2013

Asthma and COPD: Tools for Diagnosis and Differentiation

Jennifer Banfield, APRN, FNP

Clinical Research Coordinator

Boys Town National Research Hospital

Kevin R. Murphy, MD

Director of Allergy, Asthma, and

Pulmonary Research
Boys Town National Research Hospital
Department of Pediatrics
University of Nebraska Medical Center

Creighton University School of Medicine

Key Points
Asthma and chronic obstructive pulmonary disease (COPD) are both common obstructive
lung diseases and, despite sharing some key symptoms, are distinct in terms of pathogenesis
and management

In most cases, asthma, which is characterized by reversible airway obstruction on challenge

with a short-acting bronchodilator, can be differentiated from COPD, which is diagnosed on the
basis of a postbronchodilator forced expiratory volume in 1 second/forced vital capacity of
<0.7
However, persistent asthma in some cases can be associated with partially reversible airway
obstruction, which can make differential diagnosis difficult
When partially reversible airway obstruction is present, a rigorous medical history, physical
examination, questionnaire-based tools, and the use of supplementary techniques, such as
the analysis of flow-volume loops, can help distinguish between asthma and COPD
Other tools, such as spirometers, the Asthma Control Test questionnaire, and the Clinical
COPD Questionnaire, are available to facilitate the monitoring of disease progression over
time
Other articles by the same authors in this e-newsletter series:

Review of the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological
Management of Chronic Obstructive Pulmonary Disease
Original Publish Date = 6/29/2010
Available at: http://advanceweb.com/web/focus_on_copd/article2.html
Reversibility of Airflow Obstruction in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Original Publish Date = 2/11/2011
Available at: http://advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction/focus_on_copd_issue2.html

Devices for Aerosol Delivery in the Treatment of Adults With Asthma and Chronic Obstructive Pulmonary Disease
(COPD) in the United States
Original Publish Date = 7/22/2011

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Available at: http://advanceweb.com/web/AstraZeneca/focus_on_copd_issue3_DevicesForAerosol/focus_on_copd_issue3.html

Gastroesophageal Reflux Disease in Older Children and Adults With Asthma
Original Publish Date = 12/29/2011
Available at: http://www.advanceweb.com/web/AstraZeneca/focus_on_copd_issue4_Reflux/focus_on_copd_issue4.html

Do Your Patients With Asthma Exercise?

Original Publish Date = 8/2012
Available at: http://advanceweb.com/web/AstraZeneca/focus_on_copd_issue5_AsthmaExercise/focus_on_copd_issue5.html
COPD Management and the 2011 GOLD Guidelines
Original Publish Date = 3/2013
Available at: http://advanceweb.com/web/AstraZeneca/focus_on_copd_issue6_COPDMgmt/focus_on_copd_issue6.html

Introduction

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases that share key symptoms,

such as dyspnea and wheezing, but are etiologically distinct. Both asthma and COPD are characterized by airflow
limitation. Asthma is a chronic inflammatory disease of hyper-reactive airways, in which episodes are often

associated with specific triggers, such as allergens [1]. In contrast, COPD is a progressive disease characterized
by persistent airflow limitation due to chronic inflammatory response of the lungs to noxious particles or gases,
primarily caused by cigarette smoking. These differences in pathology are matched by different treatment
strategies; therefore, differential diagnosis is essential.

In addition to medical history, physical examination, and spirometry, questionnaire tools can aid diagnosis,

classification of severity, and monitoring of asthma and COPD. The basics of understanding spirometry can be
reviewed at http://www.advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction

/spirometry_module.html. Questionnaire tools include screenings for COPD (COPD Population Screener

[COPD-PS] [2], the Clinical COPD Questionnaire [CCQ] [3], and Lung Function Questionnaire [LFQ] [4]); tools to

assess the severity of asthma (National Asthma Education and Prevention Program [NAEPP] [5]); tools to monitor

disease progression and control (Asthma Control Test [ACT] [6], pediatric Test for Respiratory and Asthma Control
in Kids [TRACK] [7]); and tools to help differentiate between asthma and COPD [8, 9].

The measurement of forced expiratory volume in 1 second (FEV1) with a spirometer can also facilitate the
monitoring of both asthma and COPD in primary care. Handheld digital spirometers for office use are an

alternative to conventional spirometry for the routine monitoring of lung function. These devices have acceptable

accuracy, are easy to use, and require minimal storage space [10]. Additionally, emerging tools, such as exhaled
nitric oxide (eNO), are available and can be used in the diagnosis of asthma and differentiation between asthma

and COPD [11]. Because both asthma and COPD are highly prevalent, Nurse Practitioners are at the forefront of
diagnosing, managing, and differentiating between asthma and COPD [1].

Mark is a 48-year-old white man who is rarely seen in the clinic. However, he is becoming increasingly
worried about episodes of breathlessness, which occur 13 times a year. He shows no sign of acute
respiratory distress as he talks through his recent medical history, which includes cutting down on a

15pack year history of smoking from 1 pack per day to 12 cigarettes per week. He remembers something
from his childhood about "athletes asthma" but does not have a recent history of use of inhalers. On
questioning, he mentions an uncle with asthma.

Note: This is a hypothetical case description for teaching purposes.

Diagnosis of Asthma

An accurate diagnosis of asthma is based on a combination of medical history, physical examination, and

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spirometry [5]. A thorough medical history should include pattern of occurrence; precipitating or aggravating

factors; exacerbation type, severity, and frequency; family and social history; and the patients own assessment of
their illness.

The physical examination should be focused on abnormalities of the nose, throat, upper airway, skin, and chest
[5]. In terms of the latter, hyperexpansion of the thorax, use of accessory muscles, appearance of hunched

shoulders, and chest deformity should increase the suspicion of asthma. Auscultations of wheezing during normal
breathing and/or a prolonged phase of forced exhalation are typical findings associated with airflow obstruction.
However, the NAEPP notes that wheezing may only be heard during forced exhalation, but this is not a reliable

indicator of airflow limitation [5]. Signs of allergic reactions, such as increased nasal secretion, mucosal swelling,

and/or nasal polyps; atopic dermatitis/eczema; or any other manifestation of an allergic skin condition, should also
raise suspicion of asthma [5].

Spirometry, in combination with medical history and physical examination, is essential to establish the diagnosis of

asthma. Spirometry must establish reversible obstructive airflow defined as an increase in FEV1 of 12% and 200
mL after the administration of a bronchodilator [12]. The Global Initiative for Asthma (GINA) guidelines advise that
most asthma patients will not demonstrate reversibility at every assessment; therefore, repeat assessments are
recommended [12]. Importantly for the differential diagnosis of asthma and COPD, it should be noted that

persistent non-fully reversible airway obstruction, the classic hallmark of COPD, can also occur in patients with
long-standing asthma [13].

The NAEPP provides guidance on establishing the severity of asthma, which is based on 2 components:

impairment and risk of future adverse effects of the condition (such as exacerbations and decreasing lung

function). Both of these domains are based on spirometry, frequency of symptoms and their effect on normal

activity, and response to treatment [5]. Similarly, assessment of asthma control relies on the monitoring of the
effectiveness of interventions to reduce impairment and reduce the risk of future adverse events [5].

Diagnosis of COPD

Diagnosis of COPD relies on the clinical presentation of the patient, a detailed review of the patients medical

history, and spirometry. Key indicators include progressive dyspnea, chronic cough, chronic sputum production,

and exposure to risk factors for the disease (smoking in particular) [14]. Diagnosing COPD can be complicated by
the presence of comorbidities, especially age-related conditions such as congestive heart failure and cardiac

arrhythmia that can mimic COPD exacerbations [14]. Two validated COPD screening tools, the LFQ [4, 15] and
COPD-PS questionnaire [2], can help identify patients who are at high risk for airflow obstruction and should

undergo spirometry. Both tools comprise 5 questions relating to patients smoking history, age, and symptoms and
can also be used to identify adults with risk factors, such as smoking history or exposure to environmental or
occupational pollutants [2]. Figure 1 shows the COPD-PS tool [2].
Figure 1. The COPD-PS Tool [2].

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Martinez et al. COPD. 2008; 5(2):8595, copyright 2008, Informa Healthcare. Reproduced with permission of Informa
Healthcare [2].

Patients with scores that indicate possible COPD should undergo spirometry. According to the American Thoracic
Society/European Respiratory Society (ATS/ERS) [16], the following is required to establish a COPD diagnosis:
postbronchodilator FEV1/ forced vital capacity (FVC) ratio 0.7, demonstrating airflow limitation that is not fully
reversible.

Spirometry also establishes the severity of the disease. According to the Global Initiative for Chronic Obstructive

Lung Disease (GOLD) guidelines, FEV1 % of predicted postbronchodilator levels of 80, 50<80, 30<50, and <30
indicate mild, moderate, severe, and very severe COPD, respectively [16]. The COPD Foundation has established
a somewhat different guide. Consistent with GOLD, the postbronchodilator FEV1/FVC ratio must be <0.7, but

slightly different postbronchodilator FEV1 criteria are used. Table 1 compares the GOLD and COPD foundation

FEV1 criteria for mild, moderate, severe, and very severe COPD. The COPD Foundation guidelines also include
the further category of Spirometry Grade Undefined (SG U)undefined COPDthat includes patients with
FEV1/FVC ratio >0.7, but FEV1 <80% predicted. The COPD foundation suggests these characteristics are

consistent with restriction, muscle weakness, and other pathologies [17]. These spirometry outcomes are just 1 of
several severity domains that the COPD foundation uses to guide therapy.

Table 1. GOLD and COPD Foundation Criteria for Establishing the Severity of COPD
GOLD

Mild

COPD Foundation

All FEV1/FVC ratio <0.7 postbronchodilator FEV1 % of predicted

80%

60%

Moderate

50<80%

30%<60%

Severe

30<50%

<30%

Very severe

<30%

COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity;
GOLD, Global Initiative for Chronic Obstructive Lung Disease; SG U, Spirometry Grade Undefined.

The COPD Foundation includes a further category, SG Uundefined COPDthat includes patients with FEV1/FVC ratio
>0.7, but FEV1 <80% predicted.

Achieving Accurate Spirometry Results

An accurate diagnosis requires accurate spirometry. The ATS/ERS guidelines on acceptable maneuvers

emphasize the importance of coaching the patient. This includes aspects such as ensuring a complete inhalation

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before beginning the maneuver, prompting the patient to "blast," not just "blow," the air from their lungs, and

encouraging him/her to fully exhale [18]. A summary of the within- and between-maneuver acceptability criteria is
provided in Table 2.

Table 2. ATS/ERS Within- and Between-Maneuver Acceptability Criteria [18]

Within-maneuver criteria

Individual programs are acceptable if:

They are free from artifacts

Cough during the first second of exhalation

Glottis closure that influences the measurement

Early termination or cutoff

Effort that is not maximal throughout

Leak

Obstructed mouthpiece

They have good starts

Extrapolated volume, <5% of FVC or 0.15 L, whichever

is greater

They show satisfactory exhalation

Duration of 6 s (3 s for children) or a plateau in the

volumetime curve
or

If the subject cannot or should not continue to exhale

Between-maneuver criteria
After 3 acceptable spirograms have been obtained, apply the
following tests:

The 2 largest values of FVC must be within 0.15 L of each

other

The 2 largest values of FEV1 must be within 0.15 L of each

other

If both of these criteria are met, the test session may be

concluded

If both of these criteria are not met, continue testing until

Both of the criteria are met with analysis of additional
acceptable spirograms
or

A total of 8 tests have been performed (optional)

or

The patient/subject cannot or should not continue

Save, as a minimum, the 3 satisfactory maneuvers

ATS, American Thoracic Society; ERS, European Respiratory Society; FEV1, forced expiratory volume in 1 second; FVC,
forced vital capacity.
This presentation has not been reviewed by European Respiratory Society prior to release; therefore the European
Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising
there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J August 2005
26:319338; doi:10.1183/09031936.05.00034805 [18].

Differential Diagnosis of Partially Reversible Airway Obstruction

In a minority of patients, differentiating asthma and COPD on the basis of reversibility of airway obstruction may
not be possible, especially in patients with long-standing asthma. Findings of a recent study suggested that the

association between early-onset, current clinical asthma, and irreversible airway obstruction was equivalent to a
33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.59.3; P = 0.005) [19]. However, a detailed medical

history can help distinguish between the 2 conditions, and some key differentiating features are listed in Table 3
[1].

Table 3. Differential Diagnosis of Asthma and COPD [1]

Asthma

COPD

Onset early in life (often childhood)

Onset in mid-life

Symptoms vary from day to day

Symptoms slowly progressive

Symptoms at night/early morning

Long history of tobacco smoking

Allergy, rhinitis, and/or eczema sometimes present

Dyspnea during exercise

Family history of asthma usually present

Largely irreversible airflow limitation

Largely reversible airflow limitation

Presence of comorbidities

COPD, chronic obstructive pulmonary disease.

Reproduced with permission from Spencer and Krieger [1].

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In addition, screening questionnaires have been developed with the specific aim of aiding differentiation between

asthma and COPD [5, 7]. A simple questionnaire based on age of onset, smoking history, atopy status, and cough
quality (Table 4) correctly classified asthma or COPD in 87.4% of cases [8]. Similarly, Tinkelman et al [9] derived a
symptom-based questionnaire including age, smoking pack-years, and 8 questions including worsening cough,

breathing-related disability or hospitalization, worsening dyspnea and phlegm quantity. This tool was reported to
have a diagnostic sensitivity and specificity of 72.0 and 82.7, respectively [9].
Table 4. 4-Item Questionnaire for Differentiating Asthma and COPD
Item

Points

Age of onset, y

<20

2040

4060

>60

Atopy

Yes

No

Smoked pack-years

>0<20

2040

>40

Cough characteristics

Dry cough

No cough

Productive cough

COPD, chronic obstructive pulmonary disease.

Data from Beeh et al [8].

Scores range from 015 points, with high scores indicating COPD and low scores suggesting asthma. A cutoff score of 7
had 87.6% sensitivity and 87.2% specificity for COPD, with 87.4% classified correctly. The overlap between asthma and
COPD (score 68) comprised approximately 20% of the total population.

Marks age and smoking history raise a concern for COPD, but a score of "7" with the differentiating tool

developed by Beeh et al [8] (Table 4) suggests either coexistent disease or the need for further tests. Marks
spirometry results reveal a postbronchodilator FEV1/FVC ratio of 0.81 and FEV1 % predicted of 85.
Note: This is a hypothetical case description for teaching purposes

Further Differentiating Tests

In difficult cases, the use of flow-volume loops may aid differential diagnosis. While spirometry reports airflow over
time, the flow-volume loop depicts airflow (in liters per second) as it relates to lung volume (in liters) during

maximal inspiration from complete exhalation and during maximum expiration from complete inhalation [18].

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Flow-volume loops can show whether airflow is appropriate for a particular lung volume. Examples of normal and
abnormal flow-volume loops are shown in Figure 2 [20]. Examples of differentials that can be uncovered by

flow-volume loops include reversibility (asthma/COPD) and obstructive (asthma or COPD) versus restrictive

(pulmonary fibrosis, pneumonias, pleural effusion), or mixed (coexisting obstructive and restrictive) conditions.
Figure 2. Normal and Abnormal Flow-Volume Loops [20]

(a) A typical obstructive pattern; (b) an obstructive pattern with patchy collapse of small airways early in exhalation; (c)
example of a typical restrictive defect; and (d) example of a typical mixed (coexisting obstructive and restrictive) defect.
Solid line = predicted flow-volume curves; Dashed line = observed inspiratory and expiratory flow volume curves.

This presentation has not been reviewed by European Respiratory Society prior to release; therefore the European
Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising
there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J November 2005
26:948968; doi:10.1183/09031936.05.00035205 [20].

As shown in Figure 3, both the inspiratory and expiratory portions of the loop provide important information. In

Marks case, the expiratory portion of the loop can provide extra information. In Figure 3, the lung damage that
accompanies COPD has caused a typical angle in the slope of the expiratory phase that helps distinguish the
condition from asthma [18, 21].

Figure 3. Differences Between Asthma and COPD Flow-Volume Loops [21]

With asthma, the expiratory portion of the loop curve is typically a smooth concave shape as the airway obstruction is
relatively stable throughout expiration. With COPD, the curve is typically angled as the damaged lungs in COPD collapse
with forced expiration. Y axis = flow rate; X axis = volume from full inspiration to full expiration; dotted line = normal
flow-volume curve.
Reproduced with permission from GP-training.neta GP education and training resource [21].

Biomarkers of asthma may also aid differentiation from COPD. In a recent review, biomarkers that are already in

clinical use, along with promising biomarkers in development are summarized [22]. One of the markers discussed
is eNO, which is often higher in patients with asthma versus patients without asthma or COPD [11, 23]. In 2011,

the ATS released guidelines on the use of eNO for clinic applications, and, in summary, levels >50 ppb in adults

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indicate inflammation of the airways typical of asthma [23]. This topic will be explored in more depth in a future
newsletter.

Marks flow-volume loop results demonstrated a smooth, concave expirational portion of the loop that
normalizes postbronchodilator indicative of asthma. His eNO was 60 ppb.
Note: This is a hypothetical case description for teaching purposes

Monitoring Control and Severity

As the diagnosis of asthma has now been made, it is important to think about monitoring the progression of Marks
condition over time. The emergence of user-friendly handheld spirometers with acceptable accuracy has greatly
facilitated routine monitoring of lung function [10]. In addition to routine monitoring of lung function,

questionnaire-based tools can aid the monitoring of disease progression. For asthma, the ACT, Asthma Therapy

Assessment Questionnaire control index, and the Asthma Control Questionnaire have all been validated for use in
this regard [5]. For younger patients, the child version of ACT (C-ACT) [24] and the Test for TRACK [7] are

available. If diagnosis had been COPD, the CCQ would be an appropriate questionnaire to monitor disease
progression.

Conclusions

Asthma and COPD can be challenging to differentiate, and in a proportion of patients (especially the

elderly), the conditions can coexist [25, 26]. However, a rigorous medical history, physical examination,
use of screening tools, and appropriate lung function tests can accurately differentiate between these
conditions in most patients, allowing disease-specific management.

Acknowledgements

We thank Paul Coyle, BSc, and Cherie K. Whitmore, PharmD, MBA, of Scientific Connexions (Lyndhurst, NJ) for
medical writing support funded by AstraZeneca LP (Wilmington, DE).

References
1. Spencer P, Krieger B. The differentiation of chronic obstructive pulmonary disorder from asthma: a review of current diagnostic and treatment
recommendations. The Open Nursing Journal. 213;7:2934.
2. Martinez FJ, Raczek AE, Seifer FD, et al. Development and initial validation of a self-scored COPD Population Screener Questionnaire (COPD-PS). COPD.
2008;5:8595.
3. Cave AJ, Atkinson L, Tsiligianni IG, Kaplan AG. Assessment of COPD wellness tools for use in primary care: an IPCRG initiative. Int J Chron Obstruct Pulmon
Dis. 2012;7:447456.
4. Yawn BP, Mapel DW, Mannino DM, et al. Development of the Lung Function Questionnaire (LFQ) to identify airflow obstruction. Int J Chron Obstruct Pulmon
Dis. 2010;5:110.
5. NAEPP-2007. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the
Diagnosis and Management of Asthma. Full report 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed June 6, 2013.
6. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol.
2004;113:5965.
7. Murphy KR, Zeiger RS, Kosinski M, et al. Test for respiratory and asthma control in kids (TRACK): a caregiver-completed questionnaire for preschool-aged
children. J Allergy Clin Immunol 2009;123:833839.

6/10/2016 11:59 PM

Asthma and COPD: Tools for Diagnosis and Differentiation

9 of 9

http://www.advanceweb.com/web/astrazeneca/focus_on_copd_issue7_To...

8. Beeh KM, Kornmann O, Beier J, Ksoll M, Buhl R. Clinical application of a simple questionnaire for the differentiation of asthma and chronic obstructive
pulmonary disease. Respir Med. 2004;98:591597.
9. Tinkelman DG, Price DB, Nordyke RJ, et al. Symptom-based questionnaire for differentiating COPD and asthma. Respiration. 2006;73:296305.
10. Derom E, van Weel C, Liistro G, et al. Primary care spirometry. Eur Respir J. 2008;31:197203.
11. Fabbri LM, Romagnoli M, Corbetta L, et al. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive
pulmonary disease. Am J Respir Crit Care Med. 2003;167:418424.
12. Global Initiative for Asthma (GINA). Pocket Guide for Asthma Management and Prevention. Updated 2012. Available at: http://www.ginasthma.org/local/uploads
/files/GINA_Pocket2013_May15.pdf. Accessed July 12, 2013.
13. Guerra S, Martinez FD. Epidemiology of the origins of airflow limitation in asthma. Proc Am Thorac Soc. 2009;6:707711.
14. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of COPD. February 2013.
Available at: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013_Feb20.pdf. Accessed June 6, 2013.
15. Hanania NA, Mannino DM, Yawn BP, et al. Predicting risk of airflow obstruction in primary care: validation of the lung function questionnaire (LFQ). Respir Med.
2010;104:11601170.
16. Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur
Respir J. 2004;23:932946.
17. Rennard S, Thomashow B, Crapo J, et al. Introducing the COPD Foundation Guide for Diagnosis and Management of COPD, recommendations of the COPD
Foundation. COPD. 2013;10:378389.
18. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319338.
19. Perret JL, Dharmage SC, Matheson MC, et al. The interplay between the effects of lifetime asthma, smoking, and atopy on fixed airflow obstruction in middle
age. Am J Respir Crit Care Med. 2013;187:4248.
20. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948968.
21. GP-training.neta GP education and training resource. Interpreting Spirometry. January 2013. Available at: http://www.gp-training.net/protocol/respiratory
/copd/spirometry.htm. Accessed July 10, 2013.
22. Vijverberg SJ, Hilvering B, Raaijmakers JA, et al. Clinical utility of asthma biomarkers: from bench to bedside. Biologics. 2013;7:199210.
23. Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications.
Am J Respir Crit Care Med. 2011;184:602615.
24. Liu AH, Zeiger R, Sorkness C, et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol.
2007;119:817825.
25. de Marco R, Pesce G, Marcon A, et al. The coexistence of asthma and chronic obstructive pulmonary disease (COPD): prevalence and risk factors in young,
middle-aged and elderly people from the general population. PLoS One. 2013;8:e62985.
26. Sexton P, Black P, Wu L, et al. Fixed airflow obstruction among nonsmokers with asthma: a case-comparison study. J Asthma. 2013;50:606612.

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